A Postbiotic Derived from Lactobacillaceae Protects Intestinal Barrier Function in a Challenge Model Using Colon Organoid Tubules

Postbiotics may help strengthen intestinal barrier function. This study assessed the effects of a postbiotic derived from <i>Limosilactobacillus fermentum</i> and <i>Lactobacillus delbrueckii</i> subsp. <i>lactis</i> on epithelial barrier and cytokine production. Human-derived colon tubules were cultured on chips for 15 days. On day 8, the epithelial barrier was disrupted with 0.7 μM afatinib. Postbiotic doses of 5, 10, or 20 mg/mL were added on days 6, 8, 11, and 13. Trans-epithelial electrical resistance (TEER) was measured on days 6, 8, 11, 13, and 15, along with phase contrast imaging. Cytokine levels were measured on day 13. All three postbiotic concentrations resulted in better TEER recovery on day 15 vs. the control (<i>p</i> < 0.001). On day 13, 10 and 20 mg/mL increased TEER (<i>p</i> < 0.001), but only 20 mg/mL did on day 11 (<i>p</i> < 0.05). Phase imaging confirmed the dose-dependent effect. The 20 mg/mL dose more effectively reduced CCL2, CX3CL1, CXCL1, CXCL5, IL-8, IL-11, and IL-4 than the other doses (<i>p</i> < 0.01), and 10 mg/mL more effectively reduced CCL2, CXCL1, CXCL10, IL-10, IL-11, and IL-23 than 5 mg/mL (<i>p</i> < 0.01). In a colonic organoid model, the <i>Lactobacillaceae</i>-derived postbiotic prevented drug-induced epithelial damage, enhanced recovery, and modulated cytokine secretion towards a more anti-inflammatory profile in a dose-dependent manner.